The Latest Update on Atomic-Bomb Survivor Studies

Transcription

1 The Latest Update on Atomic-Bomb Survivor Studies Kotaro Ozasa, Yukiko Shimizu, Eric J Grant, Ritsu Sakata, Hiromi Sugiyama, Midori Soda, Kazunori Kodama Department of Epidemiology Radiation Effects Research Foundation Hiroshima, JAPAN 1

2 Subjects of Life Span Study Atomic-bomb survivors National Census in 1950: 284,000 people answered that they met A-bomb in Hiroshima/Nagasaki Master Sample: those who lived in Hiroshima/Nagasaki in 1950 (195,000) A total of 120,000 were collected by stratified sampling for exposure status Lived in Hiroshima or Nagasaki at the time of bombing <2.5 km from the hypocenters: about 54, to 10 km: about 40,000 Not in either city at the time of bombing:about 27,000 They have been followed-up since

3 Estimation of Individual Radiation Dose (Evaluation of Exposure) 3

4 Radiation from Atomic Bomb Initial Radiation At explosion (<1min) Residual Radiation Induced radiation Radioactive Fallout Factors Influencing Individual Dose from initial radiation Non-shielded dose Distance from the explosion center Shielding condition Building, Terrain Personal condition Body size, posture, direction Individual dose for 15 organs Weighted absorbed dose (neutron x10+gamma dose) 4

5 放影研 Non-Shielded Dose (Free-in-Air Tissue Kerma) by Distance from the Hypocenter by DS02(Gy) Distance (m) Neutron Hiroshima Gammaray Gammaray Total (X10 for neutron) Neutron Nagasaki Total (X10 for neutron) Young RW, et al. DS02,,

6 Estimated Individual Doses DS02 dose Hiroshima Nagasaki Total Not-in-City 20,230 6,350 26,529 <5 mgy 21,713 16,812 38, ,744 7,232 29, ,115 2,226 12, ,376 1,052 3, , , Unknown 3,449 3,621 7,070 Total 82,214 38, ,321 Brief Description 6

7 Other Risk Factors (Confounding and Interaction) Mail surveys Self-administered questionnaire Lifestyle, etc Conducted in 1965, 69, 79, 91, and Response rate; around 60% of whole LSS subjects 7

8 Results based on (LSS 14) 8

9 Follow-up, Age at bombing Total No. of subjects 17,833 17,563 10,891 12,270 13,504 14,550 86,611 + Observed person-years 910, , , , , ,079 3,294,210 No. of death* 2,200 4,887 5,178 10,410 13,397 14,548 50,620 Alive (%) 88% 72% 52% 15% 1% 0% 42% *Excluding the deletion by the authority office + Excluding NIC Ozasa K, Shimizu Y, et al, Radiat Res,

10 Analytical Models Excess relative risk (ERR) model exposed = 0 (c,s,a,b)[1+err(d,s,e,a)] Excess absolute risk (EAR) model exposed = 0 (c,s,a,b) + EAR(d,s,e,a) c: city, s: sex, a: attained age (follow-up period), b/e: birth year/ age at exposure 0 (c,s,a,b): rate at non-exposure defined by c,s,a,b Main effects of radiation ( ) and effect modification ( ) ERR, EAR = (d) (e,s,a) (d) = d (linear), d 2 (quadratic), + d 2 (linear-quadratic) (e,s,a) = exp( e) a s 10

11 ERR by Dose for All Solid Cancer, LSS, The linear (L) model provides the best fit over the fulldose range ERR/Gy=0.42 (95%CI: 0.32, 0.53) for the genderaveraged risk estimates at age 70 after radiation exposure at age 30, based on the model with effect modification by sex, age at exposure and attained age The lowest dose range with a statistically significant trend is Gy with ERR/Gy of 0.56 Estimated threshold dose is 0.0Gy and upper 95% confidence limit is 0.15Gy Ozasa K, Shimizu Y, et al, Radiat Res,

12 Modification of ERR and EAR of All Solid Cancer by Age at Exposure and Attained Age Both ERR and EAR were higher in the young at the time of the bombings ERR decreased along with attained age while EAR increased Ozasa K, Shimizu Y, et al, Radiat Res,

13 Confounding and Interaction of Radiation Effects with Life Style and Other Factors 13

14 Interaction of Radiation and Smoking on Lung Cancer Risk, Incidence, Risk of radiation for lung cancer: ERR at 1 Gy was around 0.7 in non-smokers ERR at 1 Gy was around 2.0 in light smokers who consumed 7-8 cigarettes per day (positive interaction) No additional increase in risk by radiation in heavy smokers (negative interaction, risk of lung cancer seemed to be saturated by smoking) Furukawa K, et al. Radiat Res,

15 Issues on Risk Estimation at Lowdose Radiation Exposure Small effects at low-dose levels Low power of detection needs a large number of subjects Effects of non-radiation risk factors Lifestyle such as smoking, and geographical factors Bias and confounding Proximal/high dose survivors lived in urban area in Hiroshima and rather vise versa in Nagasaki Non-differential effects (i.e., widen the confidence intervals) Interaction (i.e., alter the risks of radiation between different strata of non-radiation risk factors) Effects of residual radiation and medical radiation exposure, revision of dose estimates, etc 15

16 Non-cancer Diseases 16

17 Risk of Circulatory Diseases, Disease category (ICD-9 code) Circulatory disease ( ) No of deaths 19,054 Heart disease ( , 402, 404, ) Ischemic heart disease ( ) Myocardial infarction (410) Hypertensive heart disease (402, 404) Rheumatic heart disease ( ) Heart failure (428) Other heart diseases Hypertensive disease without heart diseases (401, 403, 405) Stroke ( ) Cerebral infarction (433, 434) Cerebral hemorrhage (431) Subarachnoid hemorrhage (430) Others or unspecified Other circulatory disease 8,463 3,252 1, ,983 1, ,622 2,659 4, , Bar shows 95% confidence intervals Heart disease and stroke as a whole had significantly increased risks Specific disease types except for hypertensive and rheumatic heart diseases had no increased risks, but rather ill-defined diseases had them Shimizu Y, et al, BMJ, 2010 (this figure was made by the presenter using the numbers in e-table) 17

18 Risk of Possible Chronic Renal Failure Death, Several diagnostic criteria of chronic kidney disease were applied and the broadest chronic renal failure had a significant risk of radiation in a quadratic model (ERR/Gy 2 =0.091, 95%CI: 0.05, 0.198) Renal dysfunction could be part of the mechanism causing increased risk after whole-body irradiation, which hypothesis deserves further study Adams MJ Y, et al, Radiat Res,

19 Issues on Circulatory Diseases Risk of radiation exposure increased for rather ill-defined diseases Additional analyses on dose-response is being investigated by disease type, study period, age at exposure, attained age, etc Prolonged effects of deterministic effects at high dose level? Confounding by socioeconomic status and other factors related to spatial distribution of survivors? Influence of changes of dominant non-cancer diseases in Japan during these decades? Suspicious underlying malignancies? Diagnostic preciseness of death certificates? These effects would be prominent especially at low-dose levels 19

20 References Ozasa K, Shimizu Y, et al. Studies of the Mortality of Atomic Bomb Survivors, Report 14, : An Overview of Cancer and Noncancer Diseases. Radiat Res 2012; 177: Young RW, Kerr GD, eds. Reassessment of the atomic bomb radiation dosimetry for Hiroshima and Nagasaki Dosimetry system Hiroshima, Japan: Radiation Effects Research Foundation; 2005 Cullings HM, et al. Dose estimation for atomic bomb survivor studies: Its evolution and present status. Radiat Res 166:219 54, Shimizu Y, et al. Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, BMJ 2010;340:b5349, doi: /bmj.b5349 Furukawa K, et al. Radiation and smoking effects on lung cancer incidence among atomicbomb survivors. Radiat Res 2010; 74: Grant EJ, et al. Effects of radiation and lifestyle factors on risks of urothelial carcinoma in the life span study of atomic bomb survivors. Radiat Res 2012; 177: Adams MJ, et al. Radiation dose associated with renal failure mortality: A potential Pathway to partially explain increased cardiovascular disease mortality observed after whole-body irradiation. Radiat Res 2012; 177: Basic Guide to Radiation and Health Sciences, basicg/basicg_e.pdf. Brief Description, 20